title: Crybb2 coding for βB2-crystallin affects sensorimotor gating and hippocampal function.
abstract: βB2-crystallin (gene symbol: Crybb2/CRYBB2) was first described as a structural protein of the ocular lens. This gene, however, is also expressed in several regions of the mammalian brain, although its function in this organ remains entirely unknown. To unravel some aspects of its function in the brain, we combined behavioral, neuroanatomical, and physiological analyses in a novel Crybb2 mouse mutant, O377. Behavioral tests with male O377 mutants revealed altered sensorimotor gating, suggesting modified neuronal functions. Since these mouse mutants also displayed reduced hippocampal size, we concentrated further investigations on the hippocampus. Free intracellular Ca(2+) levels were increased and apoptosis was enhanced in the hippocampus of O377 mutants. Moreover, the expression of the gene encoding calpain 3 (gene symbol Capn3) was elevated and the expression of genes coding for the NMDA receptor subunits was downregulated. Additionally, the number of parvalbumin-positive interneurons was decreased in the hippocampus but not in the cortex of the mutants. High-speed voltage-sensitive dye imaging demonstrated an increased translation of input-to-output neuronal activity in the dentate gyrus of this Crybb2 mutant. These results point to an important function of βB2-crystallin in the hippocampal network. They indicate pleiotropic effects of mutations in the Crybb2 gene, which previously had been considered to be specific to the ocular lens. Moreover, our results are the first to demonstrate that βB2-crystallin has a role in hippocampal function and behavioral phenotypes. This model can now be further explored by future experiments.
authors.affiliation: Institute of Developmental Genetics, Helmholtz Center Munich - National Research Center for Environmental Health, Ingolstädter Landstrasse 1, 85764, Neuherberg, Germany.
authors.forename: Minxuan
authors.initials: M
authors.lastname: Sun
authors.forename: Sabine M
authors.initials: SM
authors.lastname: Hölter
authors.forename: Jens
authors.initials: J
authors.lastname: Stepan
authors.forename: Lillian
authors.initials: L
authors.lastname: Garrett
authors.forename: Just
authors.initials: J
authors.lastname: Genius
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kremmer
authors.forename: Martin
authors.initials: M
authors.lastname: Hrabě de Angelis
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wurst
authors.forename: D Chichung
authors.initials: DC
authors.lastname: Lie
authors.forename: Laure
authors.initials: L
authors.lastname: Bally-Cuif
authors.forename: Matthias
authors.initials: M
authors.lastname: Eder
authors.forename: Dan
authors.initials: D
authors.lastname: Rujescu
authors.forename: Jochen
authors.initials: J
authors.lastname: Graw
mesh_terms: D000818:Animals; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism; D018891:Dentate Gyrus / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D005106:Exploratory Behavior; D006706:Homeostasis; D006720:Homozygote; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000473:pathology; D009929:Organ Size; D010641:Phenotype; D055139:Sensory Gating; D038206:beta-Crystallin B Chain / Q000235:genetics / Q000378:metabolism*
chemical_list: D038206:beta-Crystallin B Chain; C113634:beta-crystallin B2; D002118:Calcium